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Molecular breeding of medicinal crops and discoveries along the way - Seminar at the Department of Plant Sciences, TODAY 1PM

last modified Nov 21, 2013 10:01 AM

 

Ian A. Graham, Centre for Novel Agricultural Products,

Department of Biology, University of York, UK

From Sweet Wormwood to Opium Poppies

The Chinese medicinal plant Artemisia annua (Sweet Wormwood or Qing Hao) is the primary source of the leading anti-malarial drug artemisinin. This sesquiterpene lactone is produced in glandular secretory trichomes on the surface of leaves. With the aid of funding from the Bill & Melinda Gates Foundation we published the first genetic map of A. annua in 2010, along with quantitative trait loci accounting for much of the variation in key traits controlling artemisinin yield (Graham et al., 2010, Science, 327:328-31). This work laid the foundation for the selection of elite parents for F1 hybrid production. In 2011 the University of York signed an agreement with East West Seeds, an international seed production company, to produce and market improved hybrid seeds, the performance of which has been proven in extensive field trials carried out in East Africa, Madagascar, India and China. Enough CNAP hybrid seed has been sold in Africa in 2013 to produce over 100 million artemisinin combination therapy treatments; enabling them to produce the remedy for their own public health problem. In parallel with the production of improved hybrids we have used TILLING to identify mutations in key genes regulating other major metabolic pathways that operate in A. annua glandular trichomes. Two mutants will be described: one that is disrupted in the production of casticin – a polymethoxylated flavonoid that can accumulate in wild type A. annua leaves to levels equivalent to artemisinin; the second mutant is disrupted in the production of camphor, a monoterpene that also accumulates to levels equivalent to artemisinin in wild type trichomes.

Opium poppy (Papaver somniferum) remains one of the most important medicinal plants in the world due to the presence of a diverse set of benzylisoquinoline alkaloids with potent pharmaceutical activities, the best known of which are the morphinan subclass including codeine and morphine. Over the last five years we have been funded by GlaxoSmithKline Australia to develop new poppy varieties with improved levels of target alkaloids including noscapine, which has been used as a human cough suppressant for decades and more recently has been shown to have anticancer properties. While the biosynthesis of the morphinan alkaloids has been characterised in detail over the last 20 years, very little was known about the biosynthesis of noscapine. A major breakthrough came recently with our discovery of a cluster of ten genes encoding five different enzyme classes responsible for the production of noscapine (Winzer et al., 2012, Science, 336:1704-8). Functional characterisation of a number of these genes by virus induced gene silencing allowed a novel biosynthetic pathway to be proposed and molecular markers are now allowing the gene cluster to be selected for as a single locus in a breeding programme that is delivering new poppy varieties.